Unlocking the potential of organoids in cancer treatment and translational research: An application of cytologic techniques.

Patient-derived organoid models hold promise for advancing clinical cancer research, including diagnosis and personalized and precision medicine approaches, and cytology, in particular, plays a pivotal role in this process. These three-dimensional multicellular structures are heterogeneous, potentially maintain the cancer phenotype, and conserve the genomic, transcriptomic, and epigenomic patterns of the parental tumors. To ensure that only tumor tissue is used for organoid development, cytologic validation is necessary before initiating the process of organoid generation. Here, we explore the technology of tumor organoids and discuss the fundamental application of cytology as a simple and cost-effective approach toward organoid development. We also underscore the potential application of organoid development in drug efficacy studies for lung cancer and head and neck tumors. Additionally, we stress the importance of using fine-needle aspiration to generate tumoroids.

Potential Use of Acrocomia aculeata Pulp Oil in the Modulation of Chronic Non-communicable Diseases, Especially in Diabetes: A Systematic Review.

INTRODUCTION: The fruit oil from Acrocomia aculeata (Macauba or Bocaiuva) is highly rich in antioxidants and other bioactive compounds, emerging as a natural source of high potential for the modulation of chronic non-communicable diseases (NCDs), like diabetes. Its effects on chronic NCDs are poorly studied yet. Our review aimed to evaluate the therapeutic results of pharmaceutical preparations containing Acrocomia aculeata pulp oil that are used for chronic NCDs. METHOD: A search was performed using PICO acronyms in English, Portuguese, and Spanish languages in the MEDLINE®, PubMed, EMBASE, Scopus, LILACs, and CENTRAL Cochrane Library databases. The degree of agreement for selection and eligibility was significant (Kappa= 0.992; 95% CI: 0.988-0.996). The difference between the intervention and control groups for blood glucose reduction was 63.5 ± 69.5 mg/dL (p<0.0001). RESULT: Overall, an improvement percentage of 55.1 ± 0.1 was observed for the variables associated with chronic NCDs, which represented 89.96% of the relative risk reduction (efficacy). CONCLUSION: The Acrocomia aculeate pulp oil exhibited promising results in experimental studies for glycemic control and reduction of a specific tumor, indicating a good potential to be explored for chronic NCDs treatment.

Novel Preclinical Study of Galloylquinic Acid Compounds from Copaifera lucens with Potent Antifungal Activity against Vaginal Candidiasis Induced in a Murine Model via Multitarget Modes of Action.

Vaginal candidiasis is a medical condition characterized by the overgrowth of Candida spp. in the vaginal cavity with complex recurrent pathogenicity as well as tolerance to antifungal therapy and hence is awaiting more safe and effective treatments. This work aimed to assess the potential antifungal activity of galloylquinic acid compounds (GQAs) from Copaifera lucens leaves against vaginal Candida albicans. The antifungal susceptibility test was performed against 20 isolates of multidrug-resistant (MDR) C. albicans using agar diffusion and broth microdilution assays. The results showed that GQAs exhibited strong antagonistic activity against the test isolates, with inhibition zone diameters ranging from 26 to 38 mm and low MICs (1 to 16 µg/mL) as well as minimum fungicidal concentrations (2 to 32 µg/mL). The MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] assay confirmed the safety of GQAs against the Vero cell line, showing a 50% inhibitory concentration (IC50) of 168.17 mg/mL. A marked difference in the growth pattern of the treated and untreated pathogens was also observed, where a concentration-dependent reduction in the growth rate occurred. Moreover, a pronounced fungicidal effect was demonstrated 6 h after treatment with 1× the minimum fungicidal concentration (MFC), as evidenced by time-kill assays, where the number of survivors was decreased a 6-fold. GQAs effectively inhibited and eradicated about 80% of C. albicans biofilm at 6 µg/mL and 32 µg/mL, respectively. Interestingly, GQAs disturbed the fungal membrane integrity, induced cell lysis, and reduced the virulence factors (proteinase and phospholipase) as well as the catalase activity. Moreover, the ergosterol content in the plasma membrane decreased in a concentration-dependent manner. Additionally, the altered mitochondrial membrane potential was associated with an increased release of cytochrome c from mitochondria to the cytosol, suggesting the initiation of early apoptosis in GQA-treated cells. Transcriptional analysis revealed that all test genes encoding virulence traits, including SAP1, PLB1, LIP1, HWP1, and ALS1, were markedly downregulated in GQA-treated cells compared to the control. The in vivo murine model of vaginal candidiasis further confirmed the therapeutic activity of GQAs (4 mg/kg of body weight) against C. albicans. This work comprehensively evaluated the antifungal, antivirulence, and antibiofilm activities of GQAs against C. albicans isolates using in vitro and in vivo models, providing molecular-level insights into the antifungal mechanism of action and experimental evidence that supports the potential use of GQAs for the treatment of vaginal candidiasis. IMPORTANCE Our work presents a new perspective on the potential use of GQAs as safe and highly effective phytochemicals against MDR C. albicans. This microorganism colonizes the human vaginal epithelium, causing vaginal candidiasis, a condition characterized by recurrent pathogenicity and tolerance to traditional antifungal therapy. Based on the results of in vitro tests, our study reports GQAs antifungal modes of action. These compounds exhibited an anticandidal effect by deactivating the fungal hydrolytic enzymes, reducing ergosterol content in the plasma membrane, altering the potential of the mitochondrial membrane, and inducing apoptosis. Additionally, GQAs showed high activity in eradicating the biofilm formed by the fungus via the downregulation of HWP1, ALS, SAP, PLB, and LIP genes, which are constitutively expressed in the biofilm. In an in vivo murine model of vaginal candidiasis, GQAs further demonstrated strong evidence of their effectiveness as an antifungal therapy. In this regard, our findings provide novel insights into the potential therapeutic use of these phytoactive molecules for vaginal candidiasis treatment.

Insights on recent innovations in bladder cancer immunotherapy.

Bladder carcinoma is the most common genitourinary cancer, with a high prevalence and global incidence. In addition to early detection by cytology, the management of bladder cancer has recently advanced, not only by improvements in conventional treatments such as surgery and chemotherapy, but also through the introduction of immunotherapeutic strategies. The number of approved immunotherapeutic agents has dramatically increased, with various preclinical and clinical applications in cancer drug discovery. Some bladder cancer immunotherapies include immune checkpoint inhibitors, adoptive cell therapy, cytokine-based therapy, bispecific antibodies, and antibody-drug conjugates. This review provides an overview of some of the innovative immunotherapeutic agents approved and in development that can potentially be used in the treatment of bladder cancer.

Novel antitumor activity of the combined treatment of galloylquinic acid compounds with doxorubicin in solid Ehrlich carcinoma model via the Notch signaling pathway modulation.

AIMS: This study aims to investigate the potential synergistic effect of the combined treatment of galloylquinic acid compounds from Copaifera lucens with doxorubicin via the modulation of the Notch pathway in solid Ehrlich carcinoma-bearing mice model. MAIN METHODS: The solid tumor model was induced by subcutaneous inoculation of Ehrlich carcinoma cells in the right hind limb of mice, after serial syngeneic cell passages in the peritoneal cavity. Sixty mice were allocated into five groups including treated groups with galloylquinic acid compounds, doxorubicin, and their combination. Normal and tumor control groups were also assigned. Tissue homogenates were collected to measure the levels of the Notch-1, Hes-1, Jagged-1, TNF-α, IL-6 and VEGF, as well as SOD, MDA, and GSH. Histopathological and immunohistochemical examinations of tumor or control tissues were also performed for the levels of NF-κB p65, cyclin D1 and caspase 3 activity. KEY FINDINGS: Our results showed that the combined treatment of galloylquinic acid compounds with doxorubicin significantly decreased the levels of the Notch-1, Hes-1, Jagged-1, TNF-α, IL-6, VEGF, NF-κB p65, and cyclin D1 in tumor tissues. Moreover, the compounds induced cancer cell death as evidence by increasing the caspase 3 activity, and they possessed potent inhibitory effects on oxidative stress. SIGNIFICANCE: Galloylquinic acid compounds exhibited promising antineoplastic effects and promoted the chemosensitivity of doxorubicin, mainly by modulating the Notch signaling pathway and its downstream effectors. These compounds may be considered in solid tumors treatment for improving the efficacy and reducing the side effects of chemotherapeutic agents.

Potential of rice straw biochar, sulfur and ryegrass (Lolium perenne L.) in remediating soil contaminated with nickel through irrigation with untreated wastewater.

BACKGROUND: Untreated wastewater carries substantial amount of heavy metals and causes potential ecological risks to the environment, food quality, soil health and sustainable agriculture. METHODOLOGY: In order to reduce the incidence of nickel (Ni2+) contamination in soils, two separate experiments (incubation and greenhouse) were conducted to investigate the potentials of rice straw biochar and elemental sulfur in remediating Ni2+ polluted soil due to the irrigation with wastewater. Five incubation periods (1, 7, 14, 28 and 56 days), three biochar doses (0, 10 and 20 g kg-1 of soil) and two doses of sulfur (0 and 5 g kg-1 of soil) were used in the incubation experiment then the Ni2+ was extracted from the soil and analyzed, while ryegrass seeds Lolium perenne L. (Poales: Poaceae) and the same doses of biochar and sulfur were used in the greenhouse experiment then the plants Ni2+-uptake was determined. RESULTS: The results of the incubation experiment revealed a dose-dependent reduction of DTPA-extractable Ni2+ in soils treated with biochar. Increasing the biochar dose from 0 g kg-1 (control) to 10 or 20 g kg-1 (treatments) decreased the DTPA-extractable Ni2+ from the soil by 24.6% and 39.4%, respectively. The application of sulfur increased the Ni2+-uptake by ryegrass plant which was used as hyper-accumulator of heavy metals in the green house experiment. However, the biochar decreased the Ni2+-uptake by the plant therefore it can be used as animal feed. CONCLUSIONS: These results indicate that the biochar and sulfur could be applied separately to remediate the Ni2+-contaminated soils either through adsorbing the Ni2+ by biochar or increasing the Ni2+ availability by sulfur to be easily uptaken by the hyper-accumulator plant, and hence promote a sustainable agriculture.

Bronchoscopic management of endobronchial carcinoid presenting as asthma Mimic.

We report a 25-year-old woman with persistent dyspnea and wheezes that had been unsuccessfully treated with inhaled beta 2-agonists and steroids for about one year. Spirometry demonstrated a restrictive pattern. Chest CT demonstrated polypoidal lesion in left main bronchus. The lesion was excised via rigid bronchoscopy. Pathology showed a picture of typical bronchial carcinoid. In this patient, due to the lack of awareness, diagnosis of carcinoid was delayed for one year.

Combining PHI and miRNAs as Biomarkers in Prostate Cancer Diagnosis and Prognosis.

BACKGROUND: Prostate cancer (PC) is considered the fifth most common cancer causing death worldwide. Many studies have pointed to dysregulated microRNA (miRNA) expression in PC and their use in early detection and follow-up of the disease. In addition, the Prostate Health Index (PHI) is the FDA-approved blood test joining total, free, and -2proPSA having greater specificity than free and total PSA for assessment of PC. METHODS: In this study, we evaluated the plasma levels of miR-21and miR-221 expression using quantitative real-time polymerase chain reaction (qRT-PCR) among 100 prostate cancer patients (50 localized and 50 metastatic cases) and 50 benign prostatic hyperplasia patients in comparison to 50 normal control subjects, as well as assess-ed its diagnostic and prognostic value and its correlation with the Prostate Health Index (PHI). RESULTS: To our knowledge, we are the first study to join PHI with miRNAs in assessing PC diagnosis and progno-sis. Our results showed that adding miR-21 to PHI for detecting patients with LPC, increased the sensitivity to 95.5% at a specificity 100% (p < 0.0001). Additionally, combining miR-221 and PHI for differentiating patients with MPC, increased the sensitivity to 96.4% at a specificity 100% (p < 0.0001). CONCLUSIONS: The potentials of circulating miR-21, miR-221, and PHI serum level as biomarkers for PC have been established not only as diagnostic factors but also as prognostic markers.

Cytotoxicity of carbon nanotube variants: a comparative in vitro exposure study with A549 epithelial and J774 macrophage cells.

While production of engineered carbon nanotubes (CNTs) has escalated in recent years, knowledge of risk associated with exposure to these materials remains unclear. We report on the cytotoxicity of four CNT variants in human lung epithelial cells (A549) and murine macrophages (J774). Morphology, metal content, aggregation/agglomeration state, pore volume, surface area and modifications were determined for the pristine and oxidized single-walled (SW) and multi-walled (MW) CNTs. Cytotoxicity was evaluated by cellular ATP content, BrdU incorporation, lactate dehydrogenase (LDH) release, and CellTiter-Blue (CTB) reduction assays. All CNTs were more cytotoxic than respirable TiO2 and SiO2 reference particles. Oxidation of CNTs removed most metallic impurities but introduced surface polar functionalities. Although slopes of fold changes for cytotoxicity endpoints were steeper with J774 compared to A549 cells, CNT cytotoxicity ranking in both cell types was assay-dependent. Based on CTB reduction and BrdU incorporation, the cytotoxicity of the polar oxidized CNTs was higher compared to the pristine CNTs. In contrast, pristine CNTs were more cytotoxic than oxidized CNTs when assessed for cellular ATP and LDH. Correlation analyses between CNTs' physico-chemical properties and average relative potency revealed the impact of metal content and surface area on the potency values estimated using ATP and LDH assays, while surface polarity affected the potency values estimated from CTB and BrdU assays. We show that in order to reliably estimate the risk posed by these materials, in vitro toxicity assessment of CNTs should be conducted with well characterized materials, in multiple cellular models using several cytotoxicity assays that report on distinct cellular processes.